Palladium-N-Heterocyclic Carbene (NHC)-Catalyzed Asymmetric Synthesis of Indolines through Regiodivergent C(sp3)H Activation: Scope and DFT Study

Two bulky, chiral, monodentate N‐heterocyclic carbene ligands were applied to palladium‐catalyzed asymmetric CH arylation to incorporate C(sp3)H bond activation. Racemic mixtures of the carbamate starting materials underwent regiodivergent reactions to afford different trans‐2,3‐substituted indoli...

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Bibliographic Details
Published in:Chemistry : a European journal 2014-11, Vol.20 (46), p.15021-15030
Main Authors: Katayev, Dmitry, Larionov, Evgeny, Nakanishi, Masafumi, Besnard, Céline, Kündig, E. Peter
Format: Article
Language:English
Subjects:
Activation
Activation analysis
asymmetric catalysis
Asymmetry
Bonding
Carbenes
Chemistry
chirality
CH activation
density functional calculations
Heterocyclic aromatic compounds
Joining
Ligands
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Summary:Two bulky, chiral, monodentate N‐heterocyclic carbene ligands were applied to palladium‐catalyzed asymmetric CH arylation to incorporate C(sp3)H bond activation. Racemic mixtures of the carbamate starting materials underwent regiodivergent reactions to afford different trans‐2,3‐substituted indolines. Although this CArCalkyl coupling requires high temperatures (140–160 °C), chiral induction is high. This regiodivergent reaction, when carried out with enantiopure starting materials, can lead to single structurally different enantiopure products, depending on the catalyst chirality. The CH activation at a tertiary center was realized only in the case of a cyclopropyl group. No CH activation takes place alpha to a tertiary center. A detailed DFT study is included and analyses of methyl versus methylene versus methine CH activation is used to rationalize experimentally observed regio‐ and enantioselectivities. Overcoming inactivity: Bulky, chiral, monodentate N‐heterocyclic carbene (NHC) ligands were successfully applied to the palladium‐catalyzed, highly enantioselective CArCalkyl coupling of an unactivated C(sp3)H bond (see scheme). Readily synthesized carbamates, containing a stereogenic center, were investigated and afforded different trans‐2,3‐substituted indolines. Furthermore, a DFT study was carried out to rationalize experimentally observed regio‐ and enantioselectivities.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.201403985